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Protein

Claudin-4

Gene

CLDN4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Plays a major role in tight junction-specific obliteration of the intercellular space.By similarity

GO - Molecular functioni

  • identical protein binding Source: UniProtKB
  • structural molecule activity Source: InterPro
  • transmembrane signaling receptor activity Source: ProtInc

GO - Biological processi

  • calcium-independent cell-cell adhesion via plasma membrane cell-adhesion molecules Source: UniProtKB
  • circadian rhythm Source: Ensembl
  • establishment of skin barrier Source: UniProtKB
  • female pregnancy Source: Ensembl
  • response to progesterone Source: Ensembl
  • signal transduction Source: GOC
Complete GO annotation...

Enzyme and pathway databases

ReactomeiREACT_19373. Tight junction interactions.

Protein family/group databases

TCDBi1.H.1.1.6. the claudin tight junction (claudin) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Claudin-4
Alternative name(s):
Clostridium perfringens enterotoxin receptor
Short name:
CPE-R
Short name:
CPE-receptor
Williams-Beuren syndrome chromosomal region 8 protein
Gene namesi
Name:CLDN4
Synonyms:CPER, CPETR1, WBSCR8
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:2046. CLDN4.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 77CytoplasmicSequence Analysis
Transmembranei8 – 2821HelicalSequence AnalysisAdd
BLAST
Topological domaini29 – 8153ExtracellularSequence AnalysisAdd
BLAST
Transmembranei82 – 10221HelicalSequence AnalysisAdd
BLAST
Topological domaini103 – 11715CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei118 – 13821HelicalSequence AnalysisAdd
BLAST
Topological domaini139 – 16022ExtracellularSequence AnalysisAdd
BLAST
Transmembranei161 – 18121HelicalSequence AnalysisAdd
BLAST
Topological domaini182 – 20928CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  • apical plasma membrane Source: Ensembl
  • apicolateral plasma membrane Source: Ensembl
  • basal plasma membrane Source: Ensembl
  • bicellular tight junction Source: UniProtKB
  • integral component of plasma membrane Source: UniProtKB
  • lateral plasma membrane Source: Ensembl
  • plasma membrane Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Membrane, Tight junction

Pathology & Biotechi

Involvement in diseasei

CLDN4 is located in the Williams-Beuren syndrome (WBS) critical region. WBS results from a hemizygous deletion of several genes on chromosome 7q11.23, thought to arise as a consequence of unequal crossing over between highly homologous low-copy repeat sequences flanking the deleted region.

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi208 – 2081Y → F: Loss of phosphorylation by EPHA2. 1 Publication

Keywords - Diseasei

Williams-Beuren syndrome

Organism-specific databases

PharmGKBiPA26572.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 209209Claudin-4PRO_0000144743Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei208 – 2081Phosphotyrosine; by EPHA21 Publication

Post-translational modificationi

Phosphorylated. Phosphorylation by EPHA2 is stimulated by EFNA1 and alters interaction with TJP1.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiO14493.
PaxDbiO14493.
PRIDEiO14493.

PTM databases

PhosphoSiteiO14493.

Expressioni

Gene expression databases

BgeeiO14493.
CleanExiHS_CLDN4.
ExpressionAtlasiO14493. baseline and differential.
GenevisibleiO14493. HS.

Organism-specific databases

HPAiCAB002610.
HPA007322.

Interactioni

Subunit structurei

Directly interacts with TJP1/ZO-1, TJP2/ZO-2 and TJP3/ZO-3. Interacts with EPHA2; phosphorylates CLDN4 and may regulate tight junctions.1 Publication

Protein-protein interaction databases

BioGridi107756. 2 interactions.
IntActiO14493. 1 interaction.

Structurei

3D structure databases

ProteinModelPortaliO14493.
SMRiO14493. Positions 5-181.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 103103Interaction with EPHA2Add
BLAST
Regioni208 – 2092Interactions with TJP1, TJP2 and TJP3By similarity

Sequence similaritiesi

Belongs to the claudin family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG46413.
GeneTreeiENSGT00760000118928.
HOGENOMiHOG000220937.
HOVERGENiHBG000643.
InParanoidiO14493.
KOiK06087.
OMAiTAHNVIR.
OrthoDBiEOG79KPGQ.
PhylomeDBiO14493.
TreeFamiTF331936.

Family and domain databases

InterProiIPR006187. Claudin.
IPR003550. Claudin4.
IPR017974. Claudin_CS.
IPR004031. PMP22/EMP/MP20/Claudin.
[Graphical view]
PANTHERiPTHR12002. PTHR12002. 1 hit.
PfamiPF00822. PMP22_Claudin. 1 hit.
[Graphical view]
PRINTSiPR01077. CLAUDIN.
PR01379. CLAUDIN4.
PROSITEiPS01346. CLAUDIN. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

O14493-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MASMGLQVMG IALAVLGWLA VMLCCALPMW RVTAFIGSNI VTSQTIWEGL
60 70 80 90 100
WMNCVVQSTG QMQCKVYDSL LALPQDLQAA RALVIISIIV AALGVLLSVV
110 120 130 140 150
GGKCTNCLED ESAKAKTMIV AGVVFLLAGL MVIVPVSWTA HNIIQDFYNP
160 170 180 190 200
LVASGQKREM GASLYVGWAA SGLLLLGGGL LCCNCPPRTD KPYSAKYSAA

RSAAASNYV
Length:209
Mass (Da):22,077
Last modified:January 1, 1998 - v1
Checksum:i0659A93AA5F0E4C5
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB000712 mRNA. Translation: BAA22984.1.
BT006989 mRNA. Translation: AAP35635.1.
BC000671 mRNA. Translation: AAH00671.1.
CCDSiCCDS5560.1.
RefSeqiNP_001296.1. NM_001305.4.
UniGeneiHs.647036.
Hs.729359.

Genome annotation databases

EnsembliENST00000340958; ENSP00000342445; ENSG00000189143.
ENST00000431918; ENSP00000388639; ENSG00000189143.
ENST00000435050; ENSP00000409544; ENSG00000189143.
GeneIDi1364.
KEGGihsa:1364.
UCSCiuc003tzi.4. human.

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB000712 mRNA. Translation: BAA22984.1.
BT006989 mRNA. Translation: AAP35635.1.
BC000671 mRNA. Translation: AAH00671.1.
CCDSiCCDS5560.1.
RefSeqiNP_001296.1. NM_001305.4.
UniGeneiHs.647036.
Hs.729359.

3D structure databases

ProteinModelPortaliO14493.
SMRiO14493. Positions 5-181.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107756. 2 interactions.
IntActiO14493. 1 interaction.

Protein family/group databases

TCDBi1.H.1.1.6. the claudin tight junction (claudin) family.

PTM databases

PhosphoSiteiO14493.

Proteomic databases

MaxQBiO14493.
PaxDbiO14493.
PRIDEiO14493.

Protocols and materials databases

DNASUi1364.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000340958; ENSP00000342445; ENSG00000189143.
ENST00000431918; ENSP00000388639; ENSG00000189143.
ENST00000435050; ENSP00000409544; ENSG00000189143.
GeneIDi1364.
KEGGihsa:1364.
UCSCiuc003tzi.4. human.

Organism-specific databases

CTDi1364.
GeneCardsiGC07P073213.
HGNCiHGNC:2046. CLDN4.
HPAiCAB002610.
HPA007322.
MIMi602909. gene.
neXtProtiNX_O14493.
PharmGKBiPA26572.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG46413.
GeneTreeiENSGT00760000118928.
HOGENOMiHOG000220937.
HOVERGENiHBG000643.
InParanoidiO14493.
KOiK06087.
OMAiTAHNVIR.
OrthoDBiEOG79KPGQ.
PhylomeDBiO14493.
TreeFamiTF331936.

Enzyme and pathway databases

ReactomeiREACT_19373. Tight junction interactions.

Miscellaneous databases

ChiTaRSiCLDN4. human.
GeneWikiiCLDN4.
GenomeRNAii1364.
NextBioi5527.
PROiO14493.
SOURCEiSearch...

Gene expression databases

BgeeiO14493.
CleanExiHS_CLDN4.
ExpressionAtlasiO14493. baseline and differential.
GenevisibleiO14493. HS.

Family and domain databases

InterProiIPR006187. Claudin.
IPR003550. Claudin4.
IPR017974. Claudin_CS.
IPR004031. PMP22/EMP/MP20/Claudin.
[Graphical view]
PANTHERiPTHR12002. PTHR12002. 1 hit.
PfamiPF00822. PMP22_Claudin. 1 hit.
[Graphical view]
PRINTSiPR01077. CLAUDIN.
PR01379. CLAUDIN4.
PROSITEiPS01346. CLAUDIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Clostridium perfringens enterotoxin utilizes two structurally related membrane proteins as functional receptors in vivo."
    Katahira J., Sugiyama H., Inoue N., Horiguchi Y., Matsuda M., Sugimoto N.
    J. Biol. Chem. 272:26652-26658(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Fetal brain.
  2. "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
    Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
    Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Colon.
  4. "EphA2 phosphorylates the cytoplasmic tail of Claudin-4 and mediates paracellular permeability."
    Tanaka M., Kamata R., Sakai R.
    J. Biol. Chem. 280:42375-42382(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH EPHA2 AND TJP1, MUTAGENESIS OF TYR-208, PHOSPHORYLATION AT TYR-208 BY EPHA2.
  5. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiCLD4_HUMAN
AccessioniPrimary (citable) accession number: O14493
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: January 1, 1998
Last modified: July 22, 2015
This is version 130 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.